I argue that the FLH predicts that proteins of major importance in eukaryotes and advanced multi-cellular life forms (e.g., animals, plants) will share deep homology with proteins in prokaryotes. I have discussed this prediction with various critics of the FLH, and the most common objection seems to be that non-teleological evolution also makes this prediction. I disagree, so let me explain.

Life seems to require a minimum of about 250 genes (Koonin, Eugene V. How Many Genes Can Make a Cell: The Minimal-Gene-Set Concept, 2002. Annual Reviews Collection, NCBI) – a proto-cell would not require that many genes. Thus, it would be perfectly acceptable, under the non-teleological model, that the last common ancestor of all life forms had approximately 250 genes, add or take a few. From this small genome, gene duplication events would have occurred, subsequently followed with mutations in the new genes, leading to the origin of novel proteins. Over time, then, and through gene and genome duplication/random mutation, this small genome would evolve into larger genomes. This model is perfectly acceptable with the non-teleological hypothesis, and the non-teleological hypothesis does not predict otherwise. However, this model – where a minimal genome gradually evolves into the biological complexity we see today, through gene duplication, genome duplication, natural selection, and random mutation – is not compatible with the front-loading hypothesis. This is because front-loading requires that the first genomes have genes that would be used by later, more complex life forms. Of the 250 or so genes required by life, none of them could encode proteins that would be used later in multicellular life forms (excluding the proteins that are necessary to all life forms). A front-loading designer couldn’t possibly hope to “stack the deck” in favor of the appearance of plants and animals, for example, by starting out with a minimal genome.

Look at it this way. With a minimal genome of 250 genes that are involved in metabolism, transcription, translation, replication, etc., evolution could tinker with that genome in any way imaginable, so that you couldn’t really front-load anything at all with a minimal genome. You couldn’t anticipate the rise of animals and plants. Such a genome would not shape subsequent evolution. If the last common ancestor of all life forms had a minimal genome, and if you ran the tape of life back, and then played it again, a totally different course of evolution would result. But if you loaded LUCA with genes that could be used by animals and plants, you could predict that something analogous to animals and plants would arise. If you loaded this genome with hemoglobin, rhodopsin, tubulin, actin, epidermal growth factors, etc. – or analogs of these proteins – something analogous to animal life forms would probably result over deep-time.

Given that you couldn’t really front-load anything with a minimal genome consisting of about 250 genes, under the front-loading hypothesis, it is necessary that the LUCA contain unnecessary (but beneficial) genes that would later be exploited by more complex life forms. Non-teleological evolution does not require this. It has no goal, unlike front-loading. It tinkers with what is there – and if a minimal genome was all that was there, it would tinker around, eventually producing “endless forms most beautiful” as Darwin so famously put it. On the other hand, front-loading is goal-oriented: a minimal genome does not allow one to plan the origin of specific biological objectives.

Thus, under the front-loading hypothesis, we would predict that important proteins in eukaryotes, animals, and plants will share deep homology with unnecessary but functional proteins in prokaryotes.

Non-teleological evolution does not predict this. Non-teleological evolution could explain that observation, but it does not predict this. And this is the important point to understand. There is nothing in non-teleological evolution that requires multi-cellular proteins to share deep homology with unnecessary prokaryotic proteins – but front-loading demands this. There is nothing in non-teleological evolution that requires that the LUCA have a genome larger than the minimum genome size – but for front-loading to occur, this must be the case. I conclude, then, that this prediction is made by the front-loading hypothesis, but it is not made by non-teleological evolution, and so front-loading is certainly testable.

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There are a handful of problems with reasoning, one of the largest surely being that the last common ancestor of all extant organism needn’t be the 250 gene basic cell. Many early lineages are likely to have died off completely and a great deal of time may well have passed before two groups which survive appeared.

As such, the lca is likely to have had >250 genes, some of which could have been archaic forms of later structures thus generating a bias towards the development of such structures in later forms.

“Life seems to require a minimum of about 250 genes…Thus, it would be perfectly acceptable, under the non-teleological model, that the last common ancestor of all life forms had approximately 250 genes, add or take a few. From this small genome, gene duplication events would have occurred, subsequently followed with mutations in the new genes, leading to the origin of novel proteins. Over time, then, and through gene and genome duplication/random mutation, this small genome would evolve into larger genomes. This model is perfectly acceptable with the non-teleological hypothesis, and the non-teleological hypothesis does not predict otherwise.”

I am not arguing that the LUCA must have 250 genes. I am saying, and this is the key point, that non-teleological evolution makes no prediction regarding the number of genes in the LUCA. Under the non-teleological model, the LUCA could have 250 genes or 500 genes or 5000 genes. It does not predict any one of these. However, the front-loading hypothesis *requires* that the LUCA have significantly more than ~250 genes. I explain the rationale for this above, in my post.

In summary, the front-loading hypothesis requires that the LUCA have more than 250 genes, and thus this is a prediction of the front-loading. But non-teleological evolution doesn’t predict this.

You say that:
“As such, the lca is likely to have had >250 genes…”

Yes, and under the front-loading hypothesis this not only makes sense, it is predicted by the front-loading hypothesis. But the non-telic model doesn’t predict this. It can explain it, but it does not predict it. This is the important point to understand.

I will repeat my conclusion above with the emphasis on certain points:
“There is nothing in non-teleological evolution that *requires* multi-cellular proteins to share deep homology with unnecessary prokaryotic proteins – but *front-loading demands this*. There is nothing in non-teleological evolution that *requires* that the LUCA have a genome larger than the minimum genome size – but *for front-loading to occur, this must be the case*.”

True, whilst extremely likely given the rate at which species go extinct there is nothing about natural evolution which requires there be >250 genes (other than probability I guess).

My point, which I perhaps didn’t express clearly enough earlier, was that is a confounding variable for your hypothesis. If you were able to find these deep homologies you make reference to, or somehow discover the LUCA had >250 genes how would you distinguish between a front-loaded LUCA and one which was naturally more derived because earlier lineages had completely disappeared?

Firstly, I actually don’t think it’s even likely – from a non-teleological standpoint – for the LUCA to have more than 250 genes. There is nothing in the non-teleological model which requires that the LUCA be more than a proto-cell, and a proto-cell would have less than 250 genes; indeed, under the non-teleological model, the LUCA could easily be little more than a self-replicating RNA strand, encoding but few genes, from which the great branches of life emerged.

Having said that, you state that:…that is a confounding variable for your hypothesis. If you were able to find these deep homologies you make reference to, or somehow discover the LUCA had >250 genes how would you distinguish between a front-loaded LUCA and one which was naturally more derived because earlier lineages had completely disappeared?

But I think you’re missing the point here. The point is that the front-loading hypothesis makes a testable prediction which non-teleological evolution does not make. Thus, if we find that the LUCA had more than ~250 genes, a prediction of the front-loading hypothesis will have been successfully confirmed, regardless of the fact that at the moment we can’t tell the difference between a designed genome in the LUCA and a genome in the LUCA that had arisen through non-teleological mechanisms. On the other hand, if it is shown that the LUCA had ~250 genes or less, this prediction of the front-loading hypothesis will have been falsified, and front-loading will have been falsified as well.

I think you will agree that the front-loading hypothesis necessarily predicts that the LUCA had more than 250 genes. And I think you will also agree that non-teleological evolution makes no such prediction. Therefore, if we discover that the LUCA had more than 250 genes, I think you’d also have to agree that a prediction of the front-loading hypothesis – that non-teleological evolution does not make – has been confirmed.

I can only reiterate what I’ve said before. Although there is nothing about evolution that requires the LUCA has a specific number of genes it is extremely likely that it had >250. This is because lineages go extinct at a high frequency so it a good deal of time probably passed between the emergence of life and a creature which had 2 or more descendant lineages that survived into the modern day.

As a case study take mitochondrial eve. Although there is nothing that requires she existed at any particular point, since lineages go extinct at a high frequency she existed relatively recently, ~200 kya.

For a hypothesis to make a truly testable prediction one has to have a way of accounting for such confounding variables, for differentiating between an effect produced by the hypothesis and one produced by something else. This is why drug trials, for example, come with a placebo wing.

As such, whilst front-loading does indeed predict there would be >250 genes in the LUCA, for that prediction to be properly testable you have to have a way of differentiating between >250 genes produced by front-loading and >250 genes produced by something else, like what I mentioned at the start of this comment.

I can only reiterate what I’ve said before. Although there is nothing about evolution that requires the LUCA has a specific number of genes it is extremely likely that it had >250. This is because lineages go extinct at a high frequency so it a good deal of time probably passed between the emergence of life and a creature which had 2 or more descendant lineages that survived into the modern day.

And this is where part of our disagreement lies. It is your position that it is extremely probable, under the non-teleological model, that the LUCA had more than 250 genes. To support this contention, you cite the observation that lineages go extinct at a high frequency. But I disagree with the idea of tying this observation to the argument that the LUCA would very probably have had more than 250 genes. This is because there is nothing whatsoever stopping a simple genome consisting of, say, 20 genes (i.e., a progenote), immediately branching off into the two lineages of the Bacteria and Archaea. You say that a good deal of time probably passed between the emergence of life and a creature that had 2 descendent lineages. Yet there is no reason whatsoever, IMHO, to suppose that a good deal of time would have probably passed between the emergence of life and the origin of the LUCA of Bacteria and Archaea. A progenote with 20, 50, 100, or 250 genes could easily diverge into these lineages, very soon after its origin.

That said, I think you’d be willing to admit that the front-loading hypothesis is indeed falsifiable: if it was found that the LUCA had less than 250 genes, the FL hypothesis will have been falsified. Do you agree?

The falsifiability of front loading depends on whether there are other such mechanisms for it to take effect other than additional genes. For example, different triplets can code for the same amino acid and so the LUCA would not care which variant made up its genes. Yet beacuse they’re different they might be more likely to evolve in a different direction. TTG is more likely to become GTG than TTT because fewer changes are required, even though TTG and TTT code for the same thing.

In this manner even a minimal genome could be predisposed to go in a certain direction, allowing for front-loading. To fully falsify the idea would also require the elimination of other mechanisms by which it could work, such as the example above.

To go even further and use any findings of bias to lend support to front-loading over alternate explanations would require controlling for natural effects, like I began this conversation with. Regardless of how likely they are to occur (and I still view a LUCA having >250 genes as rather likely given that although Bacteria and Archaea could’ve differentiated early the chances of the lineage surviving would be low) they still have to be controlled for.